Project Summary Acute Kidney Injury (AKI) is a devastating complication of critical illness. In its most severe form, AKI requiring renal replacement therapy (AKI-RRT) carries a mortality rate of greater than 50%. As a result of falling glomerular filtration rate (GFR) in severe AKI, plasma uric acid (PUA) levels rise; PUA is a potential mediator of AKI complications. Mechanisms linking elevated PUA to AKI include intratubular obstruction by uric acid crystals, endothelial dysfunction, activation of the renin-angiotensin system, and exaggerated inflammatory reactions. We propose to study the significance of PUA in patients with AKI-RRT. We propose to measure PUA in 817 stored bio-samples from the Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network (ATN) study. In Aim 1 we will examine the association between PUA and pro-inflammatory markers: IL-8, IL-18, and MIF. We hypothesize higher PUA levels will be independently associated with higher levels of IL-8, IL-18, and MIF after controlling for relevant confounding variables including severity of illness and severity of AKI. In Aim 2, we will study the prospective association between PUA and adverse clinical outcomes in AKI- RRT. We hypothesize that higher PUA levels are associated with a higher 60-day mortality and longer duration of RRT independent of relevant confounding variables including severity of illness and severity of AKI.